BRPI0710231A2 - composto, composição farmacêutica, e, intermediário para a preparação de um composto - Google Patents

composto, composição farmacêutica, e, intermediário para a preparação de um composto Download PDF

Info

Publication number: BRPI0710231A2
Authority: BR; Brazil
Prior art keywords: formula; alkyl; halogens; optionally substituted; pharmaceutically acceptable
Prior art date: 2006-04-25

Application number

BRPI0710231-3A

Other languages

English (en)

Portuguese (pt)

Inventor

Leonard Larry Winneroski

Thomas Edward Mabry

Nancy June Snyder

Owen Brendan Wallace

Yanping Xu

Original Assignee

Lilly Co Eli

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2006-04-25

Filing date

2007-04-25

Publication date

2011-08-02

2007-04-25 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

2011-08-02 Publication of BRPI0710231A2 publication Critical patent/BRPI0710231A2/pt

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 142
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
238000002360 preparation method Methods 0.000 title claims description 41
239000012450 pharmaceutical intermediate Substances 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 40
229910052736 halogen Inorganic materials 0.000 claims description 136
150000002367 halogens Chemical class 0.000 claims description 86
125000000217 alkyl group Chemical group 0.000 claims description 59
150000003839 salts Chemical class 0.000 claims description 43
239000000460 chlorine Substances 0.000 claims description 32
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
229910052801 chlorine Inorganic materials 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
239000011737 fluorine Substances 0.000 claims description 9
229910052731 fluorine Inorganic materials 0.000 claims description 9
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 8
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
BCRMGEBSPHAWMU-UHFFFAOYSA-N 2-[[2,6-dichloro-4-[4-[4-(2-fluoroethyl)piperazine-1-carbonyl]phenyl]phenyl]methyl]-2-azaspiro[4.5]decan-1-one Chemical group C1CN(CCF)CCN1C(=O)C1=CC=C(C=2C=C(Cl)C(CN3C(C4(CCCCC4)CC3)=O)=C(Cl)C=2)C=C1 BCRMGEBSPHAWMU-UHFFFAOYSA-N 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
150000003951 lactams Chemical group 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
ZVCFEOHGKZODSJ-UHFFFAOYSA-N 2-[[2,6-dichloro-4-[4-[4-(trifluoromethyl)piperidine-1-carbonyl]phenyl]phenyl]methyl]-2-azaspiro[4.5]decan-1-one Chemical group C1CC(C(F)(F)F)CCN1C(=O)C1=CC=C(C=2C=C(Cl)C(CN3C(C4(CCCCC4)CC3)=O)=C(Cl)C=2)C=C1 ZVCFEOHGKZODSJ-UHFFFAOYSA-N 0.000 claims description 3
125000004193 piperazinyl group Chemical group 0.000 claims description 3
125000003386 piperidinyl group Chemical group 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 2
238000002560 therapeutic procedure Methods 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 42
206010012601 diabetes mellitus Diseases 0.000 abstract description 26
230000000694 effects Effects 0.000 abstract description 22
208000001145 Metabolic Syndrome Diseases 0.000 abstract description 18
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 18
208000008589 Obesity Diseases 0.000 abstract description 11
235000020824 obesity Nutrition 0.000 abstract description 11
206010020772 Hypertension Diseases 0.000 abstract description 8
201000001421 hyperglycemia Diseases 0.000 abstract description 8
208000031226 Hyperlipidaemia Diseases 0.000 abstract description 3
239000005557 antagonist Substances 0.000 abstract description 3
229910052740 iodine Inorganic materials 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 172
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 73
238000006243 chemical reaction Methods 0.000 description 65
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
235000019439 ethyl acetate Nutrition 0.000 description 56
-1 adamantyl acetamides Chemical class 0.000 description 43
238000003756 stirring Methods 0.000 description 43
239000002904 solvent Substances 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 36
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
239000000243 solution Substances 0.000 description 31
239000012044 organic layer Substances 0.000 description 28
208000035475 disorder Diseases 0.000 description 27
239000000047 product Substances 0.000 description 27
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 25
239000011734 sodium Substances 0.000 description 24
238000011282 treatment Methods 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 21
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
239000012043 crude product Substances 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
241000124008 Mammalia Species 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
229960000890 hydrocortisone Drugs 0.000 description 13
108090001061 Insulin Proteins 0.000 description 12
102000004877 Insulin Human genes 0.000 description 12
241001465754 Metazoa Species 0.000 description 12
239000003112 inhibitor Substances 0.000 description 12
229940125396 insulin Drugs 0.000 description 12
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
238000003556 assay Methods 0.000 description 11
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
201000001320 Atherosclerosis Diseases 0.000 description 9
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
201000010099 disease Diseases 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
238000004519 manufacturing process Methods 0.000 description 9
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 8
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 8
229960003105 metformin Drugs 0.000 description 8
239000007787 solid Substances 0.000 description 8
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 7
FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 7
MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 7
MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 7
241000699670 Mus sp. Species 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000012141 concentrate Substances 0.000 description 7
229960004544 cortisone Drugs 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
239000000284 extract Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
101000976075 Homo sapiens Insulin Proteins 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 6
230000007823 neuropathy Effects 0.000 description 6
238000010926 purge Methods 0.000 description 6
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
206010022489 Insulin Resistance Diseases 0.000 description 5
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
239000003472 antidiabetic agent Substances 0.000 description 5
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
238000000746 purification Methods 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
230000029663 wound healing Effects 0.000 description 5
UYZFAPXBVNFJFD-UHFFFAOYSA-N 2-azaspiro[4.5]decan-1-one Chemical compound O=C1NCCC11CCCCC1 UYZFAPXBVNFJFD-UHFFFAOYSA-N 0.000 description 4
REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
229910052693 Europium Inorganic materials 0.000 description 4
XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
229940100389 Sulfonylurea Drugs 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
230000002641 glycemic effect Effects 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 4
OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 4
229960000698 nateglinide Drugs 0.000 description 4
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
208000011580 syndromic disease Diseases 0.000 description 4
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MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
DVFXLNFDWATPMW-IWOKLKJTSA-N tert-butyldiphenylsilyl Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO[Si](C=2C=CC=CC=2)(C=2C=CC=CC=2)C(C)(C)C)[C@@H](OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 DVFXLNFDWATPMW-IWOKLKJTSA-N 0.000 description 1
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
150000001467 thiazolidinediones Chemical class 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000004448 titration Methods 0.000 description 1
229960002277 tolazamide Drugs 0.000 description 1
OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
229960005371 tolbutamide Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229960001729 voglibose Drugs 0.000 description 1
239000003643 water by type Substances 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
230000036642 wellbeing Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Steroid Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

BRPI0710231-3A 2006-04-25 2007-04-25 composto, composição farmacêutica, e, intermediário para a preparação de um composto BRPI0710231A2 (pt)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US74557406P	2006-04-25	2006-04-25
US60/745574		2006-04-25
PCT/US2007/067350 WO2007127763A2 (en)	2006-04-25	2007-04-25	Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1

Publications (1)

Publication Number	Publication Date
BRPI0710231A2 true BRPI0710231A2 (pt)	2011-08-02

Family

ID=38541939

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BRPI0710231-3A BRPI0710231A2 (pt)	2006-04-25	2007-04-25	composto, composição farmacêutica, e, intermediário para a preparação de um composto

Country Status (14)

Country	Link
US (1)	US7968585B2 (de)
JP (1)	JP5324427B2 (de)
CN (1)	CN101432265B (de)
AT (1)	ATE471311T1 (de)
AU (1)	AU2007244861B2 (de)
BR (1)	BRPI0710231A2 (de)
CA (1)	CA2648019C (de)
DE (1)	DE602007007211D1 (de)
DK (1)	DK2035379T3 (de)
EA (1)	EA015499B1 (de)
ES (1)	ES2344616T3 (de)
MX (1)	MX2008013650A (de)
PT (1)	PT2035379E (de)
WO (1)	WO2007127763A2 (de)

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EP2496589B1 (de)	2009-11-05	2014-03-05	Boehringer Ingelheim International GmbH	Neue chirale phosphorliganden
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WO2011107494A1 (de)	2010-03-03	2011-09-09	Sanofi	Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung
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TW201221505A (en)	2010-07-05	2012-06-01	Sanofi Sa	Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament
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TWI537258B (zh)	2010-11-05	2016-06-11	百靈佳殷格翰國際股份有限公司	六氫茚并吡啶及八氫苯并喹啉之芳基－及雜環芳基羰基衍生物
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WO2012120056A1 (de)	2011-03-08	2012-09-13	Sanofi	Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
EP2683704B1 (de)	2011-03-08	2014-12-17	Sanofi	Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
WO2012120055A1 (de)	2011-03-08	2012-09-13	Sanofi	Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
EP2766349B1 (de)	2011-03-08	2016-06-01	Sanofi	Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
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US8703807B2 (en) *	2011-03-17	2014-04-22	Hoffmann-La Roche Inc.	Azaspirodecanone compounds
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BRPI0710273A2 (pt)	2006-04-21	2011-08-09	Lilly Co Eli	composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, intermediário
ATE543798T1 (de)	2006-04-24	2012-02-15	Lilly Co Eli	Cyclohexyl-substituierte pyrrolidinone als hemmer von 11-beta-hydroxysteroiddehydrogenase 1
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2007
- 2007-04-25 US US12/297,906 patent/US7968585B2/en not_active Expired - Fee Related
- 2007-04-25 AU AU2007244861A patent/AU2007244861B2/en not_active Ceased
- 2007-04-25 CA CA2648019A patent/CA2648019C/en not_active Expired - Fee Related
- 2007-04-25 DK DK07782529.7T patent/DK2035379T3/da active
- 2007-04-25 CN CN2007800148399A patent/CN101432265B/zh not_active Expired - Fee Related
- 2007-04-25 AT AT07782529T patent/ATE471311T1/de active
- 2007-04-25 WO PCT/US2007/067350 patent/WO2007127763A2/en not_active Ceased
- 2007-04-25 ES ES07782529T patent/ES2344616T3/es active Active
- 2007-04-25 EA EA200870475A patent/EA015499B1/ru not_active IP Right Cessation
- 2007-04-25 BR BRPI0710231-3A patent/BRPI0710231A2/pt not_active IP Right Cessation
- 2007-04-25 JP JP2009507936A patent/JP5324427B2/ja not_active Expired - Fee Related
- 2007-04-25 PT PT07782529T patent/PT2035379E/pt unknown
- 2007-04-25 DE DE602007007211T patent/DE602007007211D1/de active Active
- 2007-04-25 MX MX2008013650A patent/MX2008013650A/es active IP Right Grant

Also Published As

Publication number	Publication date
WO2007127763A3 (en)	2007-12-13
DK2035379T3 (da)	2010-09-06
CN101432265B (zh)	2011-12-14
AU2007244861A1 (en)	2007-11-08
EA015499B1 (ru)	2011-08-30
JP5324427B2 (ja)	2013-10-23
WO2007127763A2 (en)	2007-11-08
CA2648019A1 (en)	2007-11-08
JP2009535357A (ja)	2009-10-01
MX2008013650A (es)	2008-11-04
US7968585B2 (en)	2011-06-28
US20090099180A1 (en)	2009-04-16
DE602007007211D1 (de)	2010-07-29
ATE471311T1 (de)	2010-07-15
CN101432265A (zh)	2009-05-13
EA200870475A1 (ru)	2009-06-30
ES2344616T3 (es)	2010-09-01
CA2648019C (en)	2014-04-01
PT2035379E (pt)	2010-07-13
AU2007244861B2 (en)	2012-03-15

Legal Events

Date	Code	Title	Description
2018-01-23	B07D	Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]
2018-04-24	B06F	Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]
2019-03-19	B08F	Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]	Free format text: REFERENTE A 12A ANUIDADE.
2019-07-02	B07E	Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]	Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI
2019-07-09	B08K	Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette]	Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2515 DE 19-03-2019 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013.

Publication	Publication Date	Title
ES2344616T3 (es)	2010-09-01	Inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1.
ES2429570T3 (es)	2013-11-15	Inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1
CA2649650C (en)	2014-01-14	Substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1
BRPI0710468A2 (pt)	2011-08-16	composto, e, composição farmacêutica
ES2336849T3 (es)	2010-04-16	Inhibidores de 11-beta-hidroxiesteroide dehidrogenasa 1.
JP5225980B2 (ja)	2013-07-03	１１−β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤としてのピエリジニル置換ピロリジノン
BRPI0710246A2 (pt)	2011-08-09	composto ou um sal farmaceuticamente aceitável do mesmo, e, composição farmacêutica.
BRPI0710467A2 (pt)	2011-08-16	composto, composição farmacêutica, uso de um composto, e, intermediário
EP2035379B1 (de)	2010-06-16	Inhibitoren von11-beta-hydroxysteroiddehydrogenase 1
ES2379606T3 (es)	2012-04-27	Pirrolidinonas sustituidas con piperidinilo como inhibidores de 11-beta-hidroxiesteroidedeshidrogenasa 1